Martin Anger ^1* Katerina Komrskova ² Ahmed Balboula ³ Paolo Rinaudo ⁴ Jason Glenn Knott ^5*

• ¹ Department of Genetics and Reproductive Biotechnologies, Veterinary Research Institute, Brno, Czechia
• ² Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
• ³ Division of Animal Sciences, University of Missouri, Columbia, Kentucky, United States
• ⁴ Department of Obstetrics Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States
• ⁵ Department of Animal Science, Michigan State University, East Lansing, United States

The fusion of an egg and a sperm triggers a complex plethora of events that will ultimately lead to the formation of a new individual. Embryonic development requires the precise orchestration of a formidable number of events. Although our knowledge of the underlying mechanisms involved has significantly increased over the last two decades, new discoveries continue to surprise us, further underlining the complexity and diversity of ontogenesis in different species. The intricacy of events that occur during early development, with the rapid changes in cellular morphology and behavior, may serve as an explanation for the frequent failure of mammalian embryos. This research topic, "Fertilization and early embryogenesis: from Research to clinical practice," is comprised of thirteen publications that cover the complexity of germ cell, embryonic, and fetal development in a diverse number of species, including mice, cattle, pigs, humans, Xenopus, and axolotls. The topics of these papers range from basic research on animal germ cells and embryos to clinical studies on human IVF embryos to placentation and postimplantation events.Five studies focused on chromosomal and epigenetic aspects of early development. These include retrospective and clinical studies in humans. In Sanovec at al., the authors identified a potential new link between chromatin defects and disturbed mobility in sperm. The interaction between the DNA packaging protein protamine 2, nuclear envelope component lamin B2/3, and the cytoskeletal protein septin 12, provide a mechanistical link between abnormal sperm chromatin condensation and altered motility in a mouse model. The authors further provided evidence that a similar connection exists in human sperm. For instance, the altered expression and localization of homologue proteins is associated with low sperm motility known as asthenozoospermia.Embryonic development is known to be prone to errors during chromosome segregation. In the study by Horakova et al., the authors showed that the spindle assembly checkpoint (SAC), a surveillance mechanism that ensures accurate chromosome attachment to spindle microtubules prior to cell division, is not utilized by early mouse embryos. Instead, the blastomeres of 2-cell embryos activate a complex known as the anaphase promoting complex (APC/C) immediately after nuclear envelope breakdown (NEBD). Therefore, the absence of SAC may partially explain the higher frequency of aneuploidy in embryos.In the study by Ma et al., the authors recruited two female patients from a family characterized by recurrent early embryo failure after IVF or ICSI. Using whole-exome sequencing on zygotes, the authors identified a mutation in a gene that encodes for regulator of G protein signaling 12 (RGS12). Phenotypic analysis of oocytes and zygotes from these patients revealed defects in calcium signaling, prolonged CSF arrest, and the inability to activate APC/C sufficiently, resulting in arrest after the 1-cell stage. The authors postulate that the RGS12 gene mutation plays a causal role in recurrent early embryo failure.Human IVF embryos can exhibit unusual patterns of cell division after IVF or ICSI such as fast cell (FC) division to the 3-cell stage via two consecutive divisions or instant direct cleavage (IDC) into 3 blastomeres. The utilization rate of embryos that exert these types of cleavage is not known. In a retrospective study by Nemerovsky et al., the authors show that although FC dividing embryos exhibited reduced development into blastocysts, the pregnancy rate was similar to controls. Most IDC embryos arrested on day 3, and those that developed into blastocysts did not produce a pregnancy. Since blastomeres resulting from fast division might be aneuploid, this illustrates that developing human embryos exhibit a surprising degree of plasticity and redundancy.The review by Montgomery et al. provides an exquisite overview of the developmental dynamics of DNA methylation and the role of ten-eleven translocation (TET) enzymes in demethylation in oocytes, preimplantation embryos, primordial germ cells, and adults. These enzymes are not only essential for epigenetic reprogramming during normal development, but their malfunction is associated with various types of cancer and developmental disorders. The authors further discuss the implications of TET enzymes in human ART.Two studies focused on the microscopic assessment of oocytes and preimplantation embryos and the impact of oil-covered culture media on the efficacy of small molecule inhibitors. Oocyte and embryo quality is paramount for their utilization in ART. However, it is not always possible to assess oocytes and early embryos without compromising the developmental potential. Thanks to the recent progress in live imaging and micromanipulation, the biomechanical properties of oocytes and embryos can be assessed using noninvasive techniques. Fluks et al. provide a comprehensive review on the biomechanical properties of oocytes and preimplantation embryos and discuss various techniques that are used to evaluate these properties.In the laboratory it is a common practice to use small molecule inhibitors to block the activity of key cell-cycle regulators and signaling proteins in oocytes and preimplantation embryos. In Rémillard-Labrosse et al., the authors demonstrated that several different inhibitors lose activity in standard oil-covered culture media, likely by partitioning into the oil. The authors conclude that researchers should be extremely cautious when using oil to culture oocytes and embryos in the presence of small molecule inhibitors and recommend using oil-free culture systems.Three studies focused on embryonic development and tetraploid complementation. In Šimková et al., the authors assessed spatiotemporal changes in expression of various transcripts during early development in axolotl. Since the localization of specific transcripts is essential for the development of the body plan, the comparison was aimed at identifying similarities and differences between axolotls and Xenopus. The authors reported surprising differences between both species. One notable difference was the development of primordial germ cells, indicating that even fundamental processes might not be conserved between closely related species.